The goal of this double-blind, six-week crossover study is to evaluate the efficacy of topiramate versus placebo in attenuating self-injurious behavior (SIB) in 10 subjects with Prader-Willi syndrome (PWS). This neurogenetic disorder, resulting from a loss of the paternal-only expressed genes on chromosome 15 (15 q11-13), is characterized with a persistent pattern of SIB, most notably skin picking, that results in frequent medical care and attention. SIB in mental retardation and related developmental disabilities are often followed by behavioral observation methods. However, there are differences between SIB forms and body locations in individuals with PWS and mental retardation and surreptitious self-injury occurring in PWS. Direct evaluation of skin lesions has been reported to help systematically follow wounds and wound healing. Therefore, in this study the investigators plan to monitor SIB by observation and photographic recordings of the resultant skin lesions, by reports of group home staff, and by standardized rating measurements of self-injury. Since PWS is a neurogenetic disorder, the investigators will also note if there are differences in response to therapy between subjects with a deletion of chromosome 15 q11-13 and those with a uniparental disomy of chromosome 15. The double-blind six-week crossover phase will be followed by a four-month open-label extension phase. Safety and efficacy measurements will be performed during the trial and in the event of a worsening of the subject's self-injury course; the blind will be broken by the trial's medical oversight physician, and if appropriate, the subject will be placed directly into the four-month open-label extension phase. A preliminary eight-week open-label study conducted to evaluate topiramate for appetite and weight in PWS by the investigators has shown good tolerability and beneficial effects. Six subjects have completed this trial and during that study an unexpected and serendipitous finding was that of these six subjects, four engaged in SIB and all four had noticeable improvement during the eight-weeks of treatment. Three of these four have continued on topiramate therapy long term with positive results in terms of decreased self-injury. Preliminary results also show no significant changes in cognitive functioning (as described using the Gordon Diagnostic System, the Controlled Oral Word Association Test, and the Semantic Category Naming test). In addition, results show an improvement in aberrant behaviors and a reduction in weight.